ArticleCell discovery2023
The Fe-S cluster assembly protein IscU2 increases α-ketoglutarate catabolism and DNA 5mC to promote tumor growth.
Article in Cell discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 21 citations in OpenAlex.
- Targeting mitochondrial α-ketoglutarate sequestration disables dual oncogenic drivers and metabolic adaptability in pancreatic ductal adenocarcinoma.Cell death & disease · 2026Article
- The role of tumor metabolic reprogramming in acquired anti-PD-1/PD-L1 resistance.Translational lung cancer research · 2026Review
- GSDME acts as an epigenetic modifier to promote melanoma development via centriole biogenesis regulator PLK4.Cell death and differentiation · 2026Article
- Review
- Prognostic value of PRAME gene promoter methylation and expression in hepatocellular carcinoma.Clinical epigenetics · 2026Article
- Ubiquitin-specific protease 11 suppresses cuproptosis in colorectal cancer by regulating the ubiquitination and stability of ISCU.Oncogenesis · 2026Article
- Regulatory networks of iron sulfur cluster biology in cancer mechanisms and therapeutic perspectives.iScience · 2026Review
- KRAS and MYC synergistic inhibition: a powerful strategy targeting KRAS-mutant cancers.Molecular cancer · 2026Review
- A novel microprotein MUCP1 promotes colorectal cancer metabolic reprogramming by regulating mitochondrial succinate transport.Neoplasia (New York, N.Y.) · 2026Article
- Regulation of mitochondrial iron homeostasis in tumor cells.Molecular medicine (Cambridge, Mass.) · 2026Review
- c-Myc/GRPEL1 maintains fatty acid synthesis via FASN to support PDAC cell proliferation.Cell death & disease · 2026Article
- Mitochondrial unfolded protein response as a central stress-integration hub: mechanisms and implications in disease contexts.Burns & trauma · 2026Review
- The integral membrane protein smim4 modulates redox balance via malate compartmentalization in pancreatic cancer.Nature communications · 2025Article
- Cuproptosis and Cardiovascular Diseases: Mechanisms, Pathophysiology, and Therapeutic Strategies-A Narrative Review.Reviews in cardiovascular medicine · 2025Review
- Mitochondrial metabolism and cancer therapeutic innovation.Signal transduction and targeted therapy · 2025Review
- Ten-Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy.MedComm · 2025Review
- Causal relationship between mitochondrial proteins and risks of aortic aneurysms and aortic dissection: a Mendelian randomization study.Journal of cardiothoracic surgery · 2025Article
- Metabolic reprogramming in cancer and senescence.MedComm · 2025Review
- Mitochondria and the Repurposing of Diabetes Drugs for Off-Label Health Benefits.International journal of molecular sciences · 2025Review
- Impaired Iron-Sulfur Cluster Synthesis Induces Mitochondrial PARthanatos in Diabetic Cardiomyopathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
IscU2 is a scaffold protein that is critical for the assembly of iron-sulfur (Fe-S) clusters and the functions of Fe-S-containing mitochondrial proteins. However, the role of IscU2 in tumor development remains unclear. Here, we demonstrated that IscU2 expression is much higher in human pancreatic ductal adenocarcinoma (PDAC) tissues than in adjacent normal pancreatic tissues. In PDAC cells, activated KRAS enhances the c-Myc-mediated IscU2 transcription. The upregulated IscU2 stabilizes Fe-S cluster and regulates the activity of tricarboxylic acid (TCA) cycle enzymes α-ketoglutarate (α-KG) dehydrogenase and aconitase 2, which promote α-KG catabolism through oxidative and reductive TCA cycling, respectively. In addition to promoting mitochondrial functions, activated KRAS-induced and IscU2-dependent acceleration of α-KG catabolism results in reduced α-KG levels in the cytosol and nucleus, leading to an increase in DNA 5mC due to Tet methylcytosine dioxygenase 3 (TET3) inhibition and subsequent expression of genes including DNA polymerase alpha 1 catalytic subunit for PDAC cell proliferation and tumor growth in mice. These findings underscore a critical role of IscU2 in KRAS-promoted α-KG catabolism, 5mC-dependent gene expression, and PDAC growth and highlight the instrumental and integrated regulation of mitochondrial functions and gene expression by IscU2 in PDAC cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.